文章：

染色质修饰因子突变；生发中心B细胞淋巴瘤新兴标志

Mutation of chromatin modifiers; an emerging hallmark of germinal center B-cell lymphomas

原文发布日期：2015-10-16

DOI: 10.1038/bcj.2015.89

类型: Original Article

开放获取: 是

英文摘要：

Subtypes of non-Hodgkin’s lymphomas align with different stages of B-cell development. Germinal center B-cell (GCB)-like diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Burkitt’s lymphoma (BL) each share molecular similarities with normal GCB cells. Recent next-generation sequencing studies have gained insight into the genetic etiology of these malignancies and revealed a high frequency of mutations within genes encoding proteins that modifying chromatin. These include activating and inactivating mutations of genes that perform post-translational modification of histones and organize chromatin structure. Here, we discuss the function of histone acetyltransferases (CREBBP, EP300), histone methyltransferases (KDM2C/D, EZH2) and regulators of higher order chromatin structure (HIST1H1C/D/E, ARID1A and SMARCA4) that have been reported to be mutated in ⩾5% of DLBCL, FL or BL. Mutations of these genes are an emerging hallmark of lymphomas with GCB-cell origins, and likely represent the next generation of therapeutic targets for these malignancies.

摘要翻译： 

非霍奇金淋巴瘤的亚型与B细胞发育的不同阶段相对应。生发中心B细胞样弥漫性大B细胞淋巴瘤、滤泡性淋巴瘤和伯基特淋巴瘤各自与正常生发中心B细胞具有分子相似性。近期新一代测序研究揭示了这些恶性肿瘤的遗传病因，并发现编码染色质修饰蛋白的基因存在高频突变。这些突变包括负责组蛋白翻译后修饰和染色质结构组织的基因激活与失活突变。本文重点探讨在≥5%的弥漫性大B细胞淋巴瘤、滤泡性淋巴瘤或伯基特淋巴瘤中存在突变的组蛋白乙酰转移酶、组蛋白甲基转移酶以及高级染色质结构调控因子的功能。这些基因突变已成为生发中心B细胞来源淋巴瘤的新兴标志，很可能成为下一代针对这类恶性肿瘤的治疗靶点。

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